The influence of laser process parameters on the densification,phase composition,microstructure,and mechanical properties of Ta−33wt.%Ti alloy prepared via laser powder bed fusion(LPBF)was investigated.The results sho...The influence of laser process parameters on the densification,phase composition,microstructure,and mechanical properties of Ta−33wt.%Ti alloy prepared via laser powder bed fusion(LPBF)was investigated.The results show that fully dense and homogeneous Ta−Ti parts can be obtained from LPBF with appropriate energy input.The cellular and dendritic structures were formed due to constitutional undercooling.Transmission electron microscopy(TEM)analysis showed that the lamellarα″phase within the cellular structures preferred to concentrate at the cellular boundaries owing to the elemental micro-segregation in the solidification front.The samples fabricated under the energy density of 166.7 J/mm^(3) had a favorable ultimate tensile strength of 806 MPa and an excellent Young’s modulus of 36.7 GPa.展开更多
AIM: To induce the tolerance of rat liver allograft by dendritic cells (DCs) modified with NF-κB decoy oligodeoxynucleotides (ODNs).METHODS: Bone marrow (BM)-derived DCs from SD rats were propagated in the presence o...AIM: To induce the tolerance of rat liver allograft by dendritic cells (DCs) modified with NF-κB decoy oligodeoxynucleotides (ODNs).METHODS: Bone marrow (BM)-derived DCs from SD rats were propagated in the presence of GM-CSF or GM-CSF+IL-4 to obtain immature DCs or mature DCs. GM-CSF+IL-4-propagated DCs were treated with double-strand NF-κB decoy ODNs containing two NF-κB binding sites or scrambled ODNs to ascertain whether NF-κB decoy ODNs might prevent DC maturation. GM-CSF-propagated DCs, GM-CSF+NF-κB decoy ODNs or scrambled ODNs-propagated DCs were treated with LPS for 18 h to determine whether NF-κB decoy ODNs could prevent LPS-induced IL-12 production in DCs. NF-κB binding activities, costimulatory molecule (CD40, CD80, CD86) surface expression, IL-12 protein expression and allostimulatory capacity of DCs were measured with electrophoretic mobility shift assay (ENSA),flow cytometry, Western blotting, and mixed lymphocyte reaction (MLR), respectively. GM-CSF-propagated DCs, GM-CSF+IL-4 -propagated DCs, and GM-CSF+NF-κB decoy ODNs or scrambled ODNs-propagated DCs were injected intravenously into recipient LEW rats 7 d prior to liver transplantation and immediately after liver transplantation.Histological grading of liver graft rejection was determined 7 d after liver transplantation. Expression of IL-2, IL-4 and IFN-γ, mRNA in liver graft and in recipient spleen was analyzed by semiquantitative RT-PCR. Apoptosis of liver allograft-infiltrating cells was measured with TUNEL staining.RESULTS: GM-CSF-propagated DCs, GM-CSF+NF-κB decoy ODNs-propagated DCs and GM-CSF+ scrambled ODNs-propagated DCs exhibited features of immature DCs, with similar low level of costimulatory molecule(CD40, CD80,CD86) surface expression, absence of NF-κB activation,and few allocostimulatory activities. GM-CSF+IL-4-propagated DCs displayed features of mature DCs, with high levels of costimulatory molecule (CD40, CD80, CD86) surface expression, marked NF-κB activation, and significant allocostimulatory activity. NF-κB decoy ODNs completely abrogated IL-4-induced DC maturation and allocostimulatory activity as well as LPS-induced NF-κB activation and IL-12 protein expression in DCs. GM-CSF+NF-κB decoy ODNs-propagated DCs promoted apoptosis of liver allograft-infiltrating cells within portal areas, and significantly decreased the expression of IL-2 and IFN-γ mRNA but markedly elevated IL-4 mRNA expression both in liverallograft and in recipient spleen, and consequently suppressed liver allograft rejection, and promoted liverallograft survival.CONCLUSION: NF-κB decoy ODNs-rnodified DCs canprolong liver allograft survival by promoting apoptosis of graft-infiltrating cells within portal areas as well as down-regulating IL-2 and IFN-γ mRNA and up-regulating IL-4 rnRNA expression both in liver graft and in recipient spleen.展开更多
AIM: To investigate the effects of dendritic cells (DCs) transfected with full-length wild-type p53 and stimulated by gastric cancer lysates on immune response.METHODS: The wild-type p53 was transduced to DCs with ade...AIM: To investigate the effects of dendritic cells (DCs) transfected with full-length wild-type p53 and stimulated by gastric cancer lysates on immune response.METHODS: The wild-type p53 was transduced to DCs with adenovirus, and the DCs were stimulated by gastric cancer lysates. The surface molecules (B7-1, B7-2, MHC-I, MHC-II) of all DCs were detected by FACS, and the ability of the DCs to induce efficient and specific immunological response inanti-^51Cr-labeled target cells was studied. BALB/c mice injected with DCs and Mk28 were established, and CTL response in mice immunized with Lywt-p53DC was evaluated.Tumor-bearing mice were treated with Lywt-p53DC.RESULTS: The surface molecules of Lywt-p53DC had a high expression of B7-1 (86.70±0.07%), B7-2 (18.77±0.08%),MHC-I (87.20±0.05%) and MHC-II (56.70±0.07%); T lymphocytes had a specific CTL lysis ability induced by Lywt-p53DC; the CTL lysis rate was as high as 81%. The immune protection of Lywtp-53DC was obvious, the tumor diameter in Lywtp-53DC group was 3.10+0.31 ram, 2.73±0.23 ram,3.70±0.07 mm on d 13, 16 and 19, respectively, which were smaller than control, DC, wtp53DC and LyDC group (P<0.05). Tumor growth rate in Lywtp53DC group was slower than that in other groups (P<0.05).CONCLUSION: DCs transfected with wild-type p53 and stimulated by gastric cancer lysates have specific CTL killing activity.展开更多
A novel inhibitory receptor of immunoglobin superfamily (IgSF), IgSF member 13 (IgSF13), has been identified from human dendritic cells (DC). IgSF13 is a type Ⅰ transmembrane protein containing an N-terminal signal p...A novel inhibitory receptor of immunoglobin superfamily (IgSF), IgSF member 13 (IgSF13), has been identified from human dendritic cells (DC). IgSF13 is a type Ⅰ transmembrane protein containing an N-terminal signal peptide, a extracellular region with a single Ig Ⅴ-like domain, a transmembrane region, and a cytoplasmic tail with two classical immunoreceptor tyrosine-based inhibitory motifs (ITIM), suggesting its inhibitory function. IgSF13 shows significant homology to human CMRF35 and pIgR. IgSF13 gene is mapped to chromosome 17q25.2, very close to that of CMRF35. IgSF13 is preferentially expressed in myelo-monocytic cells, including monocytes, monocyte-derived DC, and monocyte-related cell lines. Upon pervanadate treatment, IgSF13 was hyper-phosphorylated and associated with Src homology-2 domain-containing phosphatases SHP-1 and SHIP, but not SHP-2. The identification of IgSF13 as a novel ITIM-bearing receptor selectively expressed by DC and monocytes suggests that it may be potentially involved in the negative regulation of specific leukocyte population.展开更多
艾滋病如何毁坏免疫系统?为什么,艾滋病患者只有1%或更少的细胞携带病毒,而大量的 T 辅助细胞遭到破坏?这是有关艾滋病的最费解的迷。洛克菲勒大学(New York,NY)的研究者认为他们已经找到了谜底,并认为正在进行的工作可能已经改观了开...艾滋病如何毁坏免疫系统?为什么,艾滋病患者只有1%或更少的细胞携带病毒,而大量的 T 辅助细胞遭到破坏?这是有关艾滋病的最费解的迷。洛克菲勒大学(New York,NY)的研究者认为他们已经找到了谜底,并认为正在进行的工作可能已经改观了开发疫苗和治疗方法的前景。这些科学家发现,树枝状细胞在行使其将抗原送至 T 细胞的正常功能同时,可能拖带上了 HIV 病毒。树枝状细胞/抗原/T 细胞相互作用时,HIV 就可能到达被抗原激活的 T 细胞。活化状态的 T 细胞迅速增殖,在 HIV 病毒毁坏细胞之前,HIV 数量猛增。然而,许多问题仍不清楚,如:树枝状细胞如何携带 HIV?展开更多
Objective To explore the anti-tumor effects induced by fusion of interleukin (IL) -18 gene transfected lung cancer cell line NCI-H460 cells with dendritic cells (DC). Methods (1) DC were induced from human monoc...Objective To explore the anti-tumor effects induced by fusion of interleukin (IL) -18 gene transfected lung cancer cell line NCI-H460 cells with dendritic cells (DC). Methods (1) DC were induced from human monocytes and fused with IL-18 transfected NCI-H460 cells. Fusion was selected using MACS microbeads. (2) Four groups (group GT,group PT, group NT and group BC) were set up. T cells activated by IL-18 gene transfected fusion or pcDNA 3.1^+ vector transfected fusion and non-transfected fusion were taken as effetor cells.展开更多
Objective To study the effect of dendritic cells (DCs) transfected with sCD40-EGFP on T-cell proliferation and the cytotoxic T lymphocyte cytotoxic activity. Methods The expressing vector pEGFP-N1 /sCD40 was transfe...Objective To study the effect of dendritic cells (DCs) transfected with sCD40-EGFP on T-cell proliferation and the cytotoxic T lymphocyte cytotoxic activity. Methods The expressing vector pEGFP-N1 /sCD40 was transfected into DCs via lipofectamine reagent mediation. Peripheral blood mononuclear cells (PBMCs) from Balb/c mice as reaction cells and DCs from sCD40 transfection group,展开更多
A 45-year-old male cook was seen for the evaluation and removal of a "mole o n my eye" of steady growth during the previous 6 months. The patient stated that he had had a "brown spot" above his lef...A 45-year-old male cook was seen for the evaluation and removal of a "mole o n my eye" of steady growth during the previous 6 months. The patient stated that he had had a "brown spot" above his left eye for 17 years prior to its recent e nlargement; it was now partly blocking the vision in his left eye. He denied a h istory or family history of cutaneous tumors, including skin cancer. On examinat ion, a 2.5-cm ×.0.5-cm ×.0.8-cm, horn-like, darkly pigmented, cutaneous no dule was evident extending from the left upper eyelid downwards to below the low er eyelid (Figs 1 and 2). He also had scattered, skin-colored, 2-3-mm cystic papules on his anterior mid-chest. A shave excision specimen was obtained from the eyelid nodule. Microscopic examination demonstrated acanthosis, hyperkeratos is, and papillomatosis (Fig. 3). Large dendritic cells with abundant melanin gra nules were spread throughout the epidermis. In addition, small basaloid or spino us keratinocytes were present in the malpighian layer.展开更多
Objective To discuss the diagnosis of follicular dendritic cell sarcoma (FDCS) of the appendix, clinicopathologic features and the treatment. Methods A case of postoperative recurrent FDCS deriving from the appendix...Objective To discuss the diagnosis of follicular dendritic cell sarcoma (FDCS) of the appendix, clinicopathologic features and the treatment. Methods A case of postoperative recurrent FDCS deriving from the appendix was reported. The pathological changes and immunohistochemistry were evaluated. Results The histopathology of the specimen obtained from the recurrent tumor was identical with that of the first laparotomy. Immunohistochemically, the tumor cells were positive for CD21, CD35,展开更多
AIM: To analyze the ability of nine different potentially probiotic bacteria to induce maturation and cytokine production in human monocyte-derived dendritic cells (moDCs). METHODS: Cytokine production and maturat...AIM: To analyze the ability of nine different potentially probiotic bacteria to induce maturation and cytokine production in human monocyte-derived dendritic cells (moDCs). METHODS: Cytokine production and maturation of moDCs in response to bacterial stimulation was analyzed with enzyme-linked immunosorbent assay (ELISA) and flow cytometric analysis (FACS), respectively. The kinetics of mRNA expression of cytokine genes was determined by Northern blotting. The involvement of different signaling pathways in cytokine gene expression was studied using specific pharmacological signaling inhibitors. RESULTS: All studied bacteria induced the maturation of moDCs in a dose-dependent manner. More detailed analysis with S. thermophilus THS, B. breve Bb99, and L. lactis subsp, cremoris ARH74 indicated that these bacteria induced the expression of moDC maturation markers HLA class Ⅱ and CD86 as efficiently as pathogenic bacteria. However, these bacteria differed in their ability to induce moDC cytokine gene expression. S. thermophilus induced the expression of pro-inflammatory (TNF-α, IL-12, IL-6, and CCL20) and Thl type (IL-12 and IFN-γ) cytokines, while B. breve and L. lactis were also potent inducers of antiinflammatory IL-10. Mitogen-activated protein kinase (MAPK) p38, phosphatidylinositol 3 (PI3) kinase, and nuclear factor-kappa B (NF-κB) signaling pathways were shown to be involved in bacteria-induced cytokine production. CONCLUSION: Our results indicate that potentially probiotic bacteria are able to induce moDC maturation, but their ability to induce cytokine gene expression varies significantly from one bacterial strain to another,展开更多
Indoleamine 2, 3-dioxygenase (IDO) is a rate-limiting enzyme for the tryptophan catabolism. In human and murine cells, IDO inhibits antigen-specific T cell proliferation in vitro and suppresses T cell responses to fet...Indoleamine 2, 3-dioxygenase (IDO) is a rate-limiting enzyme for the tryptophan catabolism. In human and murine cells, IDO inhibits antigen-specific T cell proliferation in vitro and suppresses T cell responses to fetal alloantigens during murine pregnancy. In mice, IDO expression is an inducible feature of specific subsets of dendritic cells (DCs), and is important for T cell regulatory properties. However, the effect of IDO and tryptophan deprivation on DC func- tions remains unknown. We report here that when tryptophan utilization was prevented by a pharmacological inhibitor of IDO, 1-methyl tryptophan (1MT), DC activation induced by pathogenic stimulus lipopolysaccharide (LPS) or inflam- matory cytokine TNF-α was inhibited both phenotypically and functionally. Such an effect was less remarkable when DC was stimulated by a physiological stimulus, CD40 ligand. Tryptophan deprivation during DC activation also regu- lated the expression of CCR5 and CXCR4, as well as DC responsiveness to chemokines. These results suggest that tryptophan usage in the microenvironment is essential for DC maturation, and may also play a role in the regulation of DC migratory behaviors.展开更多
AIM: To investigate the in vitro effect of entecavir (ETV on the function of dendritic cells (DCs) derived from chronic hepatitis B (CHB) patients. METHODS: Mononuclear cells were isolated from peripheral blood of pat...AIM: To investigate the in vitro effect of entecavir (ETV on the function of dendritic cells (DCs) derived from chronic hepatitis B (CHB) patients. METHODS: Mononuclear cells were isolated from peripheral blood of patients with CHB. DCs wer incubated with RPMI-1640 medium supplemented wit fetal bovine serum, IL-4, granulocyte-macrophag colony-stimulating factor (GM-CSF). DCs were treate with or without ETV on the fourth day. Cell surfac molecules, including CD1a, CD80, CD83 and HLA-DR were assessed by flow cytometry. Concentrations of IL- and IL-12 in the supernatant were assayed by enzyme linked immunosorbent assay (ELISA). The ability of th generated DCs to stimulate lymphocyte proliferation wa observed. RESULTS: Compared with CHB control group, th expression levels of CD1a (29.07 ± 3.20 vs 26.85 ± 2.80 CD83 (25.66 ± 3.19 vs 23.21 ± 3.10), CD80 (28.00 ± 2.7 vs 25.75 ± 2.51) and HLA-DR (41.96 ± 3.81 vs 32.20 ± 3.04) in ETV-treated group were higher (P < 0.05). ETV treated group secreted significantly more IL-12 (157.6 ± 26.85 pg/mL vs 132.60 ± 22.00 pg/mL (P < 0.05) an had a lower level of IL-6 in the culture supernatant (83.0 ± 13.88 pg/mL vs 93.60 ± 13.61 pg/mL, P < 0.05) tha CHB control group. The ability of DCs to stimulate th proliferation of allogeneic lymphocytes was increase in ETV-treated group compared with CHB control grou (1.53 ± 0.09 vs 1.42 ± 0.08, P < 0.05).CONCLUSION: Entecavir can enhance the biological activity of DCs derived from CHB patients.展开更多
AIM: To find a novel antigen (Ag) presentation strategy to improve the immune responses induced by dendritic cell (DC)vaccine expressing hepatitis C virus (HCV) core antigen (pcDNA3HCV C-Fc) in Balb/c mice (H-2d).METH...AIM: To find a novel antigen (Ag) presentation strategy to improve the immune responses induced by dendritic cell (DC)vaccine expressing hepatitis C virus (HCV) core antigen (pcDNA3HCV C-Fc) in Balb/c mice (H-2d).METHODS: pcDNA3HCV C-Fc plasmid and eukaryotic expression vector pcDNA3 were injected into mice sc. Immune responses to pcDNA3HCV C-Fc were studied. Meanwhile the effect of pcDNA3HCV C-Fc on anti-translated subcutaneous tumor of SP2/0 cells stably expressing HCV C Ag (SP2/0-HCV C-FC) was also studied. Anti-HCV C in serum was detected by enzyme-linked immunoadsordent assay (ELISA) and HCV specific cytotoxic T lymphocyte (CTL) activity was measured by LDH release assay. After 3 wk of DNA immunization,the cells of SP2/0-HCV C-FC were inoculated into mice subcutaneously and tumor growth was measured every 5 d.The survival rate and living time of mice were also calculated.RESULTS: After 4 wk of DC immunization, the A450 nm values of sera in mice immunized with pcDNA3HCV C-Fc-DC and pcDNA3-DC were 0.56±0.17 and 0.12±0.03 respectively. The antibody titres in mice codeliveried with pcDNA3HCV C-Fc with DC were significantly higher than those of mice injected with pcDNA3-DC. The HCV specific CTL activities in mice coinjected with DC and pcDNA3HCV C-Fc or empty expression vectors were(73.2±3.1) % and (24.4±8.8) %, which were significantly higher than those of mice injected with water.The DC vaccine could evidently inhibit tumor growth, prolong the survival time of mice and improve the survival rate of mice and these effects could be improved by HCV C-Fc (pcDNA3HCV C-Fc) gene codelivered.CONCLUSION: DC vaccine has a strong antigenicity in humoral and cellular immunities, which can be promoted by transduced pcDNA3HCV C-Fc expressing HCV C or Fc.Thus, pcDNA3HCV C-Fc-transduced DCs may be a promising candidate for a CTL-based vaccine against HCV.展开更多
AIM: To disclose the mechanisms that accelerate or limit tumor invasion and metastasis in gastric cancer patients. METHODS: The heparanase expression, continuity of basement, degree of infiltration by dendritic cell...AIM: To disclose the mechanisms that accelerate or limit tumor invasion and metastasis in gastric cancer patients. METHODS: The heparanase expression, continuity of basement, degree of infiltration by dendritic cells and lymphocytes in gastric cancer tissues from 33 the early and late stage patients were examined by immunohistochemistry, in situ hybridization and transmission electron microscopy. RESULTS: Heparanase mRNA expression in the late stage patients with gastric cancer was stronger than that in the early stage gastric cancer patients. In the early stage gastric cancer tissues, basement membrane (BM) appeared intact, whereas in the late stage, discontinuous BM was often present. The density of Sl00 protein positive tumor infiltrating dendritic cells (TIDC) in the early stage gastric cancer tissues was higher than that in the late stage. The infiltrating degree of tumor infiltrating lymphocytes (TIL) in the early stage patients whose tumor tissues contained a high density of TIDC was significantly higher than that in the late stage gastric cancer tissues patients with a low density of TIDC. There were few cancer cells penetrated through the continuous BM of cancer nests in the early stage gastric cancers, but many cancer cells were found outside of the defective BM of cancer nests in the late stage. CONCLUSION: Our results suggest that strongheparanase expression is related with the degradation of BM which allows or accelerates tumor invasion and metastasis. However, high density of TIDC and degree of infiltration by TIL are associated with tumor progression in human gastric cancers.展开更多
基金supported by the National Natural Science Foundation of China(No.52271046)the Natural Science Foundation of Hunan Province,China(No.2022JJ20061)the Fund of State Key Laboratory of Powder Metallurgy,Central South University,China.
文摘The influence of laser process parameters on the densification,phase composition,microstructure,and mechanical properties of Ta−33wt.%Ti alloy prepared via laser powder bed fusion(LPBF)was investigated.The results show that fully dense and homogeneous Ta−Ti parts can be obtained from LPBF with appropriate energy input.The cellular and dendritic structures were formed due to constitutional undercooling.Transmission electron microscopy(TEM)analysis showed that the lamellarα″phase within the cellular structures preferred to concentrate at the cellular boundaries owing to the elemental micro-segregation in the solidification front.The samples fabricated under the energy density of 166.7 J/mm^(3) had a favorable ultimate tensile strength of 806 MPa and an excellent Young’s modulus of 36.7 GPa.
基金Supported by the Postdoctoral Science Foundation of China,No.2003033531
文摘AIM: To induce the tolerance of rat liver allograft by dendritic cells (DCs) modified with NF-κB decoy oligodeoxynucleotides (ODNs).METHODS: Bone marrow (BM)-derived DCs from SD rats were propagated in the presence of GM-CSF or GM-CSF+IL-4 to obtain immature DCs or mature DCs. GM-CSF+IL-4-propagated DCs were treated with double-strand NF-κB decoy ODNs containing two NF-κB binding sites or scrambled ODNs to ascertain whether NF-κB decoy ODNs might prevent DC maturation. GM-CSF-propagated DCs, GM-CSF+NF-κB decoy ODNs or scrambled ODNs-propagated DCs were treated with LPS for 18 h to determine whether NF-κB decoy ODNs could prevent LPS-induced IL-12 production in DCs. NF-κB binding activities, costimulatory molecule (CD40, CD80, CD86) surface expression, IL-12 protein expression and allostimulatory capacity of DCs were measured with electrophoretic mobility shift assay (ENSA),flow cytometry, Western blotting, and mixed lymphocyte reaction (MLR), respectively. GM-CSF-propagated DCs, GM-CSF+IL-4 -propagated DCs, and GM-CSF+NF-κB decoy ODNs or scrambled ODNs-propagated DCs were injected intravenously into recipient LEW rats 7 d prior to liver transplantation and immediately after liver transplantation.Histological grading of liver graft rejection was determined 7 d after liver transplantation. Expression of IL-2, IL-4 and IFN-γ, mRNA in liver graft and in recipient spleen was analyzed by semiquantitative RT-PCR. Apoptosis of liver allograft-infiltrating cells was measured with TUNEL staining.RESULTS: GM-CSF-propagated DCs, GM-CSF+NF-κB decoy ODNs-propagated DCs and GM-CSF+ scrambled ODNs-propagated DCs exhibited features of immature DCs, with similar low level of costimulatory molecule(CD40, CD80,CD86) surface expression, absence of NF-κB activation,and few allocostimulatory activities. GM-CSF+IL-4-propagated DCs displayed features of mature DCs, with high levels of costimulatory molecule (CD40, CD80, CD86) surface expression, marked NF-κB activation, and significant allocostimulatory activity. NF-κB decoy ODNs completely abrogated IL-4-induced DC maturation and allocostimulatory activity as well as LPS-induced NF-κB activation and IL-12 protein expression in DCs. GM-CSF+NF-κB decoy ODNs-propagated DCs promoted apoptosis of liver allograft-infiltrating cells within portal areas, and significantly decreased the expression of IL-2 and IFN-γ mRNA but markedly elevated IL-4 mRNA expression both in liverallograft and in recipient spleen, and consequently suppressed liver allograft rejection, and promoted liverallograft survival.CONCLUSION: NF-κB decoy ODNs-rnodified DCs canprolong liver allograft survival by promoting apoptosis of graft-infiltrating cells within portal areas as well as down-regulating IL-2 and IFN-γ mRNA and up-regulating IL-4 rnRNA expression both in liver graft and in recipient spleen.
文摘AIM: To investigate the effects of dendritic cells (DCs) transfected with full-length wild-type p53 and stimulated by gastric cancer lysates on immune response.METHODS: The wild-type p53 was transduced to DCs with adenovirus, and the DCs were stimulated by gastric cancer lysates. The surface molecules (B7-1, B7-2, MHC-I, MHC-II) of all DCs were detected by FACS, and the ability of the DCs to induce efficient and specific immunological response inanti-^51Cr-labeled target cells was studied. BALB/c mice injected with DCs and Mk28 were established, and CTL response in mice immunized with Lywt-p53DC was evaluated.Tumor-bearing mice were treated with Lywt-p53DC.RESULTS: The surface molecules of Lywt-p53DC had a high expression of B7-1 (86.70±0.07%), B7-2 (18.77±0.08%),MHC-I (87.20±0.05%) and MHC-II (56.70±0.07%); T lymphocytes had a specific CTL lysis ability induced by Lywt-p53DC; the CTL lysis rate was as high as 81%. The immune protection of Lywtp-53DC was obvious, the tumor diameter in Lywtp-53DC group was 3.10+0.31 ram, 2.73±0.23 ram,3.70±0.07 mm on d 13, 16 and 19, respectively, which were smaller than control, DC, wtp53DC and LyDC group (P<0.05). Tumor growth rate in Lywtp53DC group was slower than that in other groups (P<0.05).CONCLUSION: DCs transfected with wild-type p53 and stimulated by gastric cancer lysates have specific CTL killing activity.
文摘A novel inhibitory receptor of immunoglobin superfamily (IgSF), IgSF member 13 (IgSF13), has been identified from human dendritic cells (DC). IgSF13 is a type Ⅰ transmembrane protein containing an N-terminal signal peptide, a extracellular region with a single Ig Ⅴ-like domain, a transmembrane region, and a cytoplasmic tail with two classical immunoreceptor tyrosine-based inhibitory motifs (ITIM), suggesting its inhibitory function. IgSF13 shows significant homology to human CMRF35 and pIgR. IgSF13 gene is mapped to chromosome 17q25.2, very close to that of CMRF35. IgSF13 is preferentially expressed in myelo-monocytic cells, including monocytes, monocyte-derived DC, and monocyte-related cell lines. Upon pervanadate treatment, IgSF13 was hyper-phosphorylated and associated with Src homology-2 domain-containing phosphatases SHP-1 and SHIP, but not SHP-2. The identification of IgSF13 as a novel ITIM-bearing receptor selectively expressed by DC and monocytes suggests that it may be potentially involved in the negative regulation of specific leukocyte population.
文摘艾滋病如何毁坏免疫系统?为什么,艾滋病患者只有1%或更少的细胞携带病毒,而大量的 T 辅助细胞遭到破坏?这是有关艾滋病的最费解的迷。洛克菲勒大学(New York,NY)的研究者认为他们已经找到了谜底,并认为正在进行的工作可能已经改观了开发疫苗和治疗方法的前景。这些科学家发现,树枝状细胞在行使其将抗原送至 T 细胞的正常功能同时,可能拖带上了 HIV 病毒。树枝状细胞/抗原/T 细胞相互作用时,HIV 就可能到达被抗原激活的 T 细胞。活化状态的 T 细胞迅速增殖,在 HIV 病毒毁坏细胞之前,HIV 数量猛增。然而,许多问题仍不清楚,如:树枝状细胞如何携带 HIV?
文摘Objective To explore the anti-tumor effects induced by fusion of interleukin (IL) -18 gene transfected lung cancer cell line NCI-H460 cells with dendritic cells (DC). Methods (1) DC were induced from human monocytes and fused with IL-18 transfected NCI-H460 cells. Fusion was selected using MACS microbeads. (2) Four groups (group GT,group PT, group NT and group BC) were set up. T cells activated by IL-18 gene transfected fusion or pcDNA 3.1^+ vector transfected fusion and non-transfected fusion were taken as effetor cells.
文摘Objective To study the effect of dendritic cells (DCs) transfected with sCD40-EGFP on T-cell proliferation and the cytotoxic T lymphocyte cytotoxic activity. Methods The expressing vector pEGFP-N1 /sCD40 was transfected into DCs via lipofectamine reagent mediation. Peripheral blood mononuclear cells (PBMCs) from Balb/c mice as reaction cells and DCs from sCD40 transfection group,
文摘A 45-year-old male cook was seen for the evaluation and removal of a "mole o n my eye" of steady growth during the previous 6 months. The patient stated that he had had a "brown spot" above his left eye for 17 years prior to its recent e nlargement; it was now partly blocking the vision in his left eye. He denied a h istory or family history of cutaneous tumors, including skin cancer. On examinat ion, a 2.5-cm ×.0.5-cm ×.0.8-cm, horn-like, darkly pigmented, cutaneous no dule was evident extending from the left upper eyelid downwards to below the low er eyelid (Figs 1 and 2). He also had scattered, skin-colored, 2-3-mm cystic papules on his anterior mid-chest. A shave excision specimen was obtained from the eyelid nodule. Microscopic examination demonstrated acanthosis, hyperkeratos is, and papillomatosis (Fig. 3). Large dendritic cells with abundant melanin gra nules were spread throughout the epidermis. In addition, small basaloid or spino us keratinocytes were present in the malpighian layer.
文摘Objective To discuss the diagnosis of follicular dendritic cell sarcoma (FDCS) of the appendix, clinicopathologic features and the treatment. Methods A case of postoperative recurrent FDCS deriving from the appendix was reported. The pathological changes and immunohistochemistry were evaluated. Results The histopathology of the specimen obtained from the recurrent tumor was identical with that of the first laparotomy. Immunohistochemically, the tumor cells were positive for CD21, CD35,
基金The Medical Research Council of the Academy of Finland and the Sigrid Juselius Foundation
文摘AIM: To analyze the ability of nine different potentially probiotic bacteria to induce maturation and cytokine production in human monocyte-derived dendritic cells (moDCs). METHODS: Cytokine production and maturation of moDCs in response to bacterial stimulation was analyzed with enzyme-linked immunosorbent assay (ELISA) and flow cytometric analysis (FACS), respectively. The kinetics of mRNA expression of cytokine genes was determined by Northern blotting. The involvement of different signaling pathways in cytokine gene expression was studied using specific pharmacological signaling inhibitors. RESULTS: All studied bacteria induced the maturation of moDCs in a dose-dependent manner. More detailed analysis with S. thermophilus THS, B. breve Bb99, and L. lactis subsp, cremoris ARH74 indicated that these bacteria induced the expression of moDC maturation markers HLA class Ⅱ and CD86 as efficiently as pathogenic bacteria. However, these bacteria differed in their ability to induce moDC cytokine gene expression. S. thermophilus induced the expression of pro-inflammatory (TNF-α, IL-12, IL-6, and CCL20) and Thl type (IL-12 and IFN-γ) cytokines, while B. breve and L. lactis were also potent inducers of antiinflammatory IL-10. Mitogen-activated protein kinase (MAPK) p38, phosphatidylinositol 3 (PI3) kinase, and nuclear factor-kappa B (NF-κB) signaling pathways were shown to be involved in bacteria-induced cytokine production. CONCLUSION: Our results indicate that potentially probiotic bacteria are able to induce moDC maturation, but their ability to induce cytokine gene expression varies significantly from one bacterial strain to another,
文摘Indoleamine 2, 3-dioxygenase (IDO) is a rate-limiting enzyme for the tryptophan catabolism. In human and murine cells, IDO inhibits antigen-specific T cell proliferation in vitro and suppresses T cell responses to fetal alloantigens during murine pregnancy. In mice, IDO expression is an inducible feature of specific subsets of dendritic cells (DCs), and is important for T cell regulatory properties. However, the effect of IDO and tryptophan deprivation on DC func- tions remains unknown. We report here that when tryptophan utilization was prevented by a pharmacological inhibitor of IDO, 1-methyl tryptophan (1MT), DC activation induced by pathogenic stimulus lipopolysaccharide (LPS) or inflam- matory cytokine TNF-α was inhibited both phenotypically and functionally. Such an effect was less remarkable when DC was stimulated by a physiological stimulus, CD40 ligand. Tryptophan deprivation during DC activation also regu- lated the expression of CCR5 and CXCR4, as well as DC responsiveness to chemokines. These results suggest that tryptophan usage in the microenvironment is essential for DC maturation, and may also play a role in the regulation of DC migratory behaviors.
文摘AIM: To investigate the in vitro effect of entecavir (ETV on the function of dendritic cells (DCs) derived from chronic hepatitis B (CHB) patients. METHODS: Mononuclear cells were isolated from peripheral blood of patients with CHB. DCs wer incubated with RPMI-1640 medium supplemented wit fetal bovine serum, IL-4, granulocyte-macrophag colony-stimulating factor (GM-CSF). DCs were treate with or without ETV on the fourth day. Cell surfac molecules, including CD1a, CD80, CD83 and HLA-DR were assessed by flow cytometry. Concentrations of IL- and IL-12 in the supernatant were assayed by enzyme linked immunosorbent assay (ELISA). The ability of th generated DCs to stimulate lymphocyte proliferation wa observed. RESULTS: Compared with CHB control group, th expression levels of CD1a (29.07 ± 3.20 vs 26.85 ± 2.80 CD83 (25.66 ± 3.19 vs 23.21 ± 3.10), CD80 (28.00 ± 2.7 vs 25.75 ± 2.51) and HLA-DR (41.96 ± 3.81 vs 32.20 ± 3.04) in ETV-treated group were higher (P < 0.05). ETV treated group secreted significantly more IL-12 (157.6 ± 26.85 pg/mL vs 132.60 ± 22.00 pg/mL (P < 0.05) an had a lower level of IL-6 in the culture supernatant (83.0 ± 13.88 pg/mL vs 93.60 ± 13.61 pg/mL, P < 0.05) tha CHB control group. The ability of DCs to stimulate th proliferation of allogeneic lymphocytes was increase in ETV-treated group compared with CHB control grou (1.53 ± 0.09 vs 1.42 ± 0.08, P < 0.05).CONCLUSION: Entecavir can enhance the biological activity of DCs derived from CHB patients.
基金Supported by the National Natural Science Foundation of China, No.30170822
文摘AIM: To find a novel antigen (Ag) presentation strategy to improve the immune responses induced by dendritic cell (DC)vaccine expressing hepatitis C virus (HCV) core antigen (pcDNA3HCV C-Fc) in Balb/c mice (H-2d).METHODS: pcDNA3HCV C-Fc plasmid and eukaryotic expression vector pcDNA3 were injected into mice sc. Immune responses to pcDNA3HCV C-Fc were studied. Meanwhile the effect of pcDNA3HCV C-Fc on anti-translated subcutaneous tumor of SP2/0 cells stably expressing HCV C Ag (SP2/0-HCV C-FC) was also studied. Anti-HCV C in serum was detected by enzyme-linked immunoadsordent assay (ELISA) and HCV specific cytotoxic T lymphocyte (CTL) activity was measured by LDH release assay. After 3 wk of DNA immunization,the cells of SP2/0-HCV C-FC were inoculated into mice subcutaneously and tumor growth was measured every 5 d.The survival rate and living time of mice were also calculated.RESULTS: After 4 wk of DC immunization, the A450 nm values of sera in mice immunized with pcDNA3HCV C-Fc-DC and pcDNA3-DC were 0.56±0.17 and 0.12±0.03 respectively. The antibody titres in mice codeliveried with pcDNA3HCV C-Fc with DC were significantly higher than those of mice injected with pcDNA3-DC. The HCV specific CTL activities in mice coinjected with DC and pcDNA3HCV C-Fc or empty expression vectors were(73.2±3.1) % and (24.4±8.8) %, which were significantly higher than those of mice injected with water.The DC vaccine could evidently inhibit tumor growth, prolong the survival time of mice and improve the survival rate of mice and these effects could be improved by HCV C-Fc (pcDNA3HCV C-Fc) gene codelivered.CONCLUSION: DC vaccine has a strong antigenicity in humoral and cellular immunities, which can be promoted by transduced pcDNA3HCV C-Fc expressing HCV C or Fc.Thus, pcDNA3HCV C-Fc-transduced DCs may be a promising candidate for a CTL-based vaccine against HCV.
文摘AIM: To disclose the mechanisms that accelerate or limit tumor invasion and metastasis in gastric cancer patients. METHODS: The heparanase expression, continuity of basement, degree of infiltration by dendritic cells and lymphocytes in gastric cancer tissues from 33 the early and late stage patients were examined by immunohistochemistry, in situ hybridization and transmission electron microscopy. RESULTS: Heparanase mRNA expression in the late stage patients with gastric cancer was stronger than that in the early stage gastric cancer patients. In the early stage gastric cancer tissues, basement membrane (BM) appeared intact, whereas in the late stage, discontinuous BM was often present. The density of Sl00 protein positive tumor infiltrating dendritic cells (TIDC) in the early stage gastric cancer tissues was higher than that in the late stage. The infiltrating degree of tumor infiltrating lymphocytes (TIL) in the early stage patients whose tumor tissues contained a high density of TIDC was significantly higher than that in the late stage gastric cancer tissues patients with a low density of TIDC. There were few cancer cells penetrated through the continuous BM of cancer nests in the early stage gastric cancers, but many cancer cells were found outside of the defective BM of cancer nests in the late stage. CONCLUSION: Our results suggest that strongheparanase expression is related with the degradation of BM which allows or accelerates tumor invasion and metastasis. However, high density of TIDC and degree of infiltration by TIL are associated with tumor progression in human gastric cancers.